The INSPIRE Study: Probable Benefit of the Neuro-Spinal Scaffold for Treatment of AIS A Thoracic Acute Spinal Cord Injury

The INSPIRE Study: InVivo Study of Probable Benefit of the Neuro-Spinal Scaffold(TM) for Safety and Neurologic Recovery in Subjects With Complete Thoracic AIS A Spinal Cord Injury

Status

Terminated

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02138110

Enrollment

Registered

2014-05-14

Start date

2014-10-13

Completion date

2023-12-31

Last updated

2024-01-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Traumatic Thoracic Acute Spinal Cord Injury

Keywords

Spinal Cord Injury (SCI), Complete (AIS A) Traumatic Acute Spinal Cord Injury

Brief summary

Detailed description

This is an HDE probable benefit, open-label, non-randomized, single-arm, multicenter study to evaluate the safety and probable benefit of the poly(lactic-co-glycolic acid)-b-poly(L-lysine) Scaffold (Scaffold) in subjects with thoracic AIS A traumatic spinal cord injury at neurological level of injury of T2-T12. The study will be conducted by qualified Investigators who have been trained on the surgical Scaffold implant procedure in order to enroll subjects in the Primary Endpoint Analysis Set, defined as all subjects with a successful Scaffold implant, no major protocol deviations, and a complete 6-month Primary Endpoint Follow-up Visit. After receiving the Scaffold and following discharge, subjects will participate in a comprehensive rehabilitation program. For the first 24-months after implantation of the Scaffold, Follow-up and Long-term Follow-up assessments will be conducted at either the study site or the rehabilitation center. The Long-term Follow-up annual visits for years 3 through 10 will be conducted over the telephone.

Interventions

DEVICENeuro-Spinal Scaffold

Implantation of a Neuro-Spinal Scaffold into the epicenter of the post-irrigation contusion cavity during open spine surgery

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

16 Years to 70 Years

Healthy volunteers

Inclusion criteria

Subjects must meet all of the following to be considered eligible: 1. AIS A classification of traumatic spinal cord injury at T2-T12 neurological level of injury confirmed by a qualified medical professional 2. Recent injury (must receive Scaffold within 7 days from injury) 3. Non-penetrating SCI (contusion injury) that is no less than approximately 4 mm in diameter by MRI 4. Requires open spine surgery allowing access to the injured spinal cord (subjects requiring either posterior surgical approach or posterior plus anterior approach will be eligible) 5. Informed consent obtained 6. 16-70 years of age, inclusive 7. Hemodynamically stable and deemed a suitable candidate for surgery

Exclusion criteria

Subjects who meet any of the following will be excluded: 1. Terminally ill subjects not likely to be able to participate in follow-up 2. Incomplete spinal cord injury (AIS B, C, D, and E injuries) 3. Subjects with more than one discrete spinal cord injury (contusion) will be excluded. 4. No discrete cavity (existing or created by irrigation/myelotomy) in the contused spinal cord in which a Scaffold can be placed 5. Evidence of clear and significant Somatosensory Evoked Potentials (SSEP) transmission through the injury site before Scaffold implantation (based on the judgment of the Investigator) 6. Subjects with clinically significant pre-existing neurological comorbidities that are unrelated to the contusion being treated (e.g., multiple sclerosis, amyotrophic lateral sclerosis, significant prior peripheral nerve dysfunction, residual problems related to previous spine-related neurological pathologies) will be excluded only if it is felt that these preexisting morbidities will increase risk, affect safety monitoring, or confound study results 7. Spinal cord injury associated with significant traumatic brain injury or coma that, in the opinion of the Investigator, would preclude adequate assessment of spinal cord function, brain injury that could be associated on its own with sensory or motor deficits, or subjects with any other reason that results in an unreliable International Standards of Neurological Classification of Spinal Cord Injury (ISNCSCI) exam 8. Subjects with clinically significant pre-existing respiratory disease not related to the contusion being treated (e.g., chronic obstructive pulmonary disorder) 9. Subjects requiring Long-term ongoing mechanical ventilation 10. Subjects with documented immune deficiency disorders, including a known diagnosis of HIV infection/AIDS 11. Recent (according to Diagnostic and Statistical Manual of Mental Disorders (DSM) IV or DSM V criteria) history of abuse of narcotics or other significant substance abuse 12. Significant injury complications where, in the view of the Investigator, participation in the study could further complicate subject care, limit study follow-up, or confound interpretation of safety or efficacy data. 13. A female who is: * Pregnant, or planning to become pregnant within the next 12-months; or * Breastfeeding; or * A woman of child-bearing potential (defined as post menarche and biologically capable of becoming pregnant \[i.e., not surgically sterile\]) who is engaged in active heterosexual relations and is not willing to use a barrier or hormonal form of birth control for 12-months following Scaffold implantation (e.g., oral, injected, or implanted contraceptives) 14. A male who is engaged in active heterosexual relations and is not willing to use birth control for 3-months following Scaffold implantation including sperm donation or banking 15. Current or impending incarceration 16. Complete spinal cord transection 17. Subjects with spinal cord injuries directly due to gunshot, knife, or other penetrating wounds. 18. Known hypersensitivity to poly(lactic-co-glycolic acid) (PLGA) or poly-L-lysine (PLL) (e.g., hypersensitivity to absorbable sutures containing PLGA) 19. History of severe mental illness (according to DSM IV or V) 20. Evidence of pre-trauma active local or systemic infection 21. Participation in another interventional clinical trial for six months after Scaffold implantation 22. Body mass index (BMI) over 39 23. Having a medical condition (e.g., cardiovascular disease, life threatening injuries), or receiving medical treatment, or having any other reason that, in the judgment of the Investigator, precludes successful participation and follow-up for at least six months or confounds collection or interpretation of study safety, feasibility, or efficacy data

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Patients With Improvement in AIS Grade of One or More Levels	6 months post-implantation	The ASIA (American Spinal Injury Association) Impairment Scale (AIS) classifies spinal cord injuries as follows: A = Complete: no sensory or motor function is preserved in the sacral segments S4-S5 B = Sensory incomplete: sensory but not motor function is preserved below the neurological level and includes the sacral segments S4-S5, AND no motor function is preserved more than three levels below the motor level on either side of the body C = Motor incomplete: motor function is preserved below the neurological level, and more than half of key muscle functions below the single neurological level of injury have a muscle grade less than 3 (Grades 0-2) D = Motor incomplete: at least half (half or more) of key muscle functions below the NLI have a muscle grade \>3 E = Normal The confirmatory ISNCSCI exam performed within 8 hours prior to surgery was used as the baseline visit.

Secondary

Measure	Time frame	Description
Number of Participants Stratified by Change From Baseline in ISNCSCI Sensory Pin Prick Score	6 months post-implantation	International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Sensory Pin Prick Scores were assessed on a scale from 0 to 2 for each sensory point tested on each side of the body (maximum score = 112), with higher scores indicating better neurologic function. The confirmatory ISNCSCI exam performed within 8 hours prior to surgery was used as the baseline visit. An improvement in pin prick score indicates an increase in score from baseline at 6-months A deterioration in pin prick score indicates a decrease in score from baseline at 6-months No change in pin prick score indicates no change in score from baseline at 6-months
Number of Participants Stratified by Change From Baseline in ISNCSCI Sensory Light Touch Score	6 months post-implantation	International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Sensory Light Touch Scores were assessed on a scale from 0 to 2 for each sensory point tested on each side of the body (maximum score = 112), with higher scores indicating better neurologic function. The confirmatory ISNCSCI exam performed within 8 hours prior to surgery was used as the baseline visit. An improvement in light touch score indicates an increase in light touch score from baseline at 6-months A deterioration in light touch score indicates a decrease in light touch score from baseline at 6-months No change in light touch score indicates no change in light touch score from baseline at 6-months
Number of Participants Stratified by Change From Baseline in Neurological Level of Injury (NLI) at 6 Months	6 months post-implantation	The neurological level of injury (NLI) refers to the most caudal segment of the spinal cord with normal sensory and antigravity motor function on both sides of the body, provided that there is normal (intact) sensory and motor function rostrally. A caudal change is an improvement in NLI whereas a rostral change is a deterioration in NLI. The confirmatory ISNCSCI exam performed within 8 hours prior to surgery was used as the baseline visit.
Number of Participants Stratified by Change From Baseline in Spinal Cord Anatomy - Cyst (Presence or Absence)	6 months post-implantation	Characteristics of spinal cord anatomy were assessed by a Board-certified neuroradiologist central reader including presence or absence of intraparenchymal cysts. Screening MRI was used as the baseline value.
Number of Participants Stratified by Change From Baseline in Spinal Cord Anatomy - Spinal Cord Adhesion (Presence or Absence)	6 months post-implantation	Characteristics of spinal cord anatomy were assessed by a Board-certified neuroradiologist central reader including the presence or absence of spinal cord adhesion. Screening MRI was used as the baseline value.
Change From Baseline in ISNCSCI Total Motor Score	6 months post-implantation	International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Total Motor Scores were assessed on a scale from 0 to 5 for each myotome tested on each side of the body (upper limb maximum score = 50 and lower limb maximum score = 50), with higher scores indicating better neurologic function. The confirmatory ISNCSCI exam performed within 8 hours prior to surgery was used as the baseline visit. An improvement in motor score indicates an increase in motor score from baseline at 6-months A deterioration in motor score indicates an decrease in motor score from baseline at 6-months No change in motor score indicates no change in motor score from baseline at 6-months

Countries

United States

Participant flow

Participants by arm

Arm	Count
Neuro-Spinal Scaffold Implantation of neuro-spinal scaffold in a cavity at the epicenter of the spinal cord contusion during open spine surgery. Neuro-Spinal Scaffold	20
Total	20

Withdrawals & dropouts

Period	Reason	FG000
Enrolled for Scaffold Implantation	Physician Decision	1
Overall Scaffold Implantation	Death	3

Baseline characteristics

Characteristic	Neuro-Spinal Scaffold
Age, Continuous	36 years
Body Mass Index	28 kg/m^2
Cause of Injury Fall	5 Participants
Cause of Injury Other-All Terrain Vehicle	1 Participants
Cause of Injury Vehicular	14 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Height	172 cm
Race/Ethnicity, Customized Race American Indian or Alaskan Native	1 Participants
Race/Ethnicity, Customized Race Black or African American	2 Participants
Race/Ethnicity, Customized Race Other	1 Participants
Race/Ethnicity, Customized Race White	16 Participants
Sex: Female, Male Female	4 Participants
Sex: Female, Male Male	16 Participants
Weight	83 kg

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	3 / 19
other Total, other adverse events	19 / 19
serious Total, serious adverse events	19 / 19

Outcome results

Primary

Percentage of Patients With Improvement in AIS Grade of One or More Levels

The ASIA (American Spinal Injury Association) Impairment Scale (AIS) classifies spinal cord injuries as follows: A = Complete: no sensory or motor function is preserved in the sacral segments S4-S5 B = Sensory incomplete: sensory but not motor function is preserved below the neurological level and includes the sacral segments S4-S5, AND no motor function is preserved more than three levels below the motor level on either side of the body C = Motor incomplete: motor function is preserved below the neurological level, and more than half of key muscle functions below the single neurological level of injury have a muscle grade less than 3 (Grades 0-2) D = Motor incomplete: at least half (half or more) of key muscle functions below the NLI have a muscle grade \>3 E = Normal The confirmatory ISNCSCI exam performed within 8 hours prior to surgery was used as the baseline visit.